Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion

Baldus, Stephan; Heitzer, Thomas; Eiserich, Jason P.; Lau, Denise; Mollnau, Hanke; Ortak, Michelle; Petri, Susan; Goldmann, Britta; Duchstein, Hans Jürgen; Berger, Jürgen; Helmchen, U.; Freeman, Bruce Α.; Meinertz, Thomas; Münzel, Thomas

doi:10.1016/j.freeradbiomed.2004.06.003

Cited by 124 publications

(74 citation statements)

References 31 publications

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“…Several lines of evidences indicate that MPO may be a metabolic "sink" for several types of ROS, including superoxide and H 2 O 2 , and may, therefore, compromise NO bioavailability. 13,58 Previous reports 58,59 have associated MPO deficiency with increased levels of pulmonary iNOS expression and NO production. Also, iNOS expression is considerably greater in Mpo Ϫ/Ϫ mice than in healthy mice (Figure 8).…”

Section: Discussionmentioning

confidence: 98%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

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Section: Discussionmentioning

confidence: 98%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

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“…Interestingly, increased MPO levels are also observed in states of diseases believed to be unrelated to microbial infection, i.e., ischemia and reperfusion injury and acute coronary disease (29)(30)(31)(32)(33). In this regard, MPO has long been attributed to tissue injury, primarily through generation of oxidants.…”

Section: Discussionmentioning

confidence: 99%

Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins

Lau

Mollnau

Eiserich

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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387

309

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Recruitment and activation of polymorphonuclear neutrophils (PMNs) reflects a primary immunological response to invading pathogens and has also emerged as a hallmark of vascular inflammation. One of the principal enzymes released upon PMN activation is myeloperoxidase (MPO), a heme protein that not only generates cytotoxic oxidants but also impacts deleteriously on nitric oxide-dependent signaling cascades within the vasculature. Because MPO also associates with the membrane of PMN, we evaluated whether MPO could also function as an autocrine modulator of PMN activation. The extent of PMN membrane-associated MPO was elevated in patients with acute inflammatory vascular disease compared with healthy individuals. Isolated PMNs bound free MPO by a CD11b͞CD18 integrin-dependent mechanism. PMNs exposed to MPO were characterized by increased tyrosine phosphorylation and p38 mitogen-activated protein kinase activation. Also, nuclear translocation of NF B in PMN was enhanced after incubation with MPO, as was surface expression of CD11b. Binding of PMN to MPO-coated fibronectin surfaces amplified PMN degranulation, as evidenced by increased release of MPO and elastase. MPO also augmented PMN-dependent superoxide (O 2 •؊ ) production, which was prevented by anti-CD11b antibodies, but not MPO inhibitors. Collectively, these results reveal that binding of MPO to CD11b͞CD18 integrins stimulates PMN signaling pathways to induce PMN activation in a mechanism independent of MPO catalytic activity. These cytokine-like properties of MPO thus represent an additional dimension of the proinflammatory actions of MPO in vascular disease.atherosclerosis ͉ cytokine ͉ endothelium ͉ leukocyte ͉ nitric oxide

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“…• NO-liberating acetylcholine inversely correlates with MPO plasma concentrations [84]. Suggesting that MPO promotes endothelial dysfunction in inflammatory vascular disease by enhancing the catabolism of…”

Section: Promotion Of Endothelial Dysfunctionmentioning

confidence: 99%

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

et al. 2016

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Atherosclerosis is the main pathophysiological process underlying coronary artery disease (CAD). Acute complications of atherosclerosis, such as myocardial infarction, are caused by the rupture of vulnerable atherosclerotic plaques, which are characterized by thin, highly inflamed, and collagen-poor fibrous caps. Several lines of evidence mechanistically link the heme peroxidase myeloperoxidase (MPO), inflammation as well as acute and chronic manifestations of atherosclerosis. MPO and MPO-derived oxidants have been shown to contribute to the formation of foam cells, endothelial dysfunction and apoptosis, the activation of latent matrix metalloproteinases, and the expression of tissue factor that can promote the development of vulnerable plaque. As such, detection, quantification and imaging of MPO mass and activity have become useful in cardiac risk stratification, both for disease assessment and in the identification of patients at risk of plaque rupture. This review summarizes the current knowledge about the role of MPO in CAD with a focus on its possible roles in plaque rupture and recent advances to quantify and image MPO in plasma and atherosclerotic plaques.

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Myeloperoxidase enhances nitric oxide catabolism during myocardial ischemia and reperfusion

Cited by 124 publications

References 31 publications

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

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